Clinical efficacy of photodynamic therapy

OBJECTIVE: The management of cervical intraepithelial neoplasia (CIN) and early invasive cancer of the uterine cervix is very difficult to approach, especially in case of young woman who wants to preserve her fertility. Conization of the cervix may have various kinds of disadvantage. The objective of this clinical retrospective study is to investigate the therapeutic effects and clinical efficacy of photodynamic therapy (PDT) including combined chemo-photodynamic therapy in patients with pre-malignant CIN and malignant invasive cervical cancer. METHODS: Total number of PDT trial case was 50 cases and total number of patient was 22 patients who registered to PDT clinic. We used photogem sensitizer and 632 nm diode laser in early two cases. After then we performed PDT using photofrin sensitizer and 630 nm diode laser in other cases. We used flat-cut, microlens, cylindrical diffuser, and interstitial type optic fibers in order to irradiate the lesions. 240 J/cm² energy was irradiated to the lesions. RESULTS: CIN 2 were 4 cases (18.2%) and CIN 3 were 15 (68.2%) and invasive cervical cancer were 3 (13.6%). Complete remission (CR) was found in 20 patients (91%). One case of 19 patients with CIN lesion recurred at 18 months after PDT treatment. CR was found in 18 cases in the patients with CIN lesions (95%). CR was found in 2 cases in the patients with invasive cervical cancer (67%). CONCLUSION: Our data showed that CR rate was fantastic in CIN group (95%). This study suggests that PDT can be recommended as new optimistic management modality on the patients with pre-malignant CIN lesions including carcinoma in situ and relatively early invasive cancer of the uterine cervix. Combined chemo-photodynamic therapy is essential in case of invasive cervical cancer. For the young age group who desperately want to preserve their fertility and have a healthy baby, PDT can be a beacon of hope.

Advance in Photosensitizers and Light Delivery for Photodynamic Therapy

The brief history of photodynamic therapy (PDT) research has been focused on photosensitizers (PSs) and light delivery was introduced recently. The appropriate PSs were developed from the first generation PS Photofrin (QLT) to the second (chlorins or bacteriochlorins derivatives) and third (conjugated PSs on carrier) generations PSs to overcome undesired disadvantages, and to increase selective tumor accumulation and excellent targeting. For the synthesis of new chlorin PSs chlorophyll a is isolated from natural plants or algae, and converted to methyl pheophorbide a (MPa) as an important starting material for further synthesis. MPa has various active functional groups easily modified for the preparation of different kinds of PSs, such as methyl pyropheophorbide a, purpurin-18, purpurinimide, and chlorin e6 derivatives. Combination therapy, such as chemotherapy and photothermal therapy with PDT, is shortly described here. Advanced light delivery system is shown to establish successful clinical applications of PDT. Phtodynamic efficiency of the PSs with light delivery was investigated in vitro and/or in vivo.

Photodynamic Therapy for Barrett's Esophagus and Esophageal Carcinoma

This paper reviews the use of photodynamic therapy (PDT) in patients with Barrett's esophagus and esophageal carcinoma. We describe the history of PDT, mechanics, photosensitizers for PDT in patients with esophageal disease. Finally, we discuss its utility and limitations in this setting.

A Case of Benign Biliary Stricture as a Complication of Photodynamic Therapy for Biliary Papillomatosis / 대한소화기내시경학회지

Biliary papillomatosis is a rare disease with a high risk of recurrence and malignant transformation. Therapeutic options include partial hepatectomy, Whipple's procedure and liver transplantation. If there is no surgical option left due to several reasons, local palliative procedures such as biliary stenting and drainage for the treatment of cholestasis are considered, but tumor growth cannot be influenced. Photodynamic therapy might be a new additional, palliative option for patients with biliary papillomatosis who are not eligible for surgery. Benign biliary stricture is a rare complication of photodynamic therapy. We report here a case of a 63-year-old male who developed benign biliary stricture after photodynamic therapy using the photosensitizer photofrin.

A Case of Early Esophageal Cancer Treated by Photodynamic Therapy in a Patient with Liver Cirrhosis Accompanied by Esophageal Varix / 대한소화기내시경학회지

Photodynamic therapy (PDT) is a non-invasive treatment for cancer that works through a photochemical effect after the administration of a photosensitizer. At first, PDT had been used for the relief of obstructive symptoms caused by exophytic esophageal cancer or for control of tumor overgrowth. Recently, several investigators have reported the use of PDT in early esophageal cancer with encouraging results. This report describes a case of a 52-year-old man with early esophageal cancer, who had a long history of liver cirrhosis with esophageal varix. The patient was treated successfully with PDT using porfimer sodium as the photosensitizer. PDT is an alternative to surgical treatment of early esophageal cancer, especially in patients with liver cirrhosis.

A case of photosensitivity reaction after photodynamic therapy for biliary papillomatosis / 대한내과학회지

Photodynamic therapy has been widely used in the treatment of various cancerous diseases. However, photodynamic therapy with a photosensitizer can cause a photosensitivity reaction on the skin. We report a case of a 64-year-old woman diagnosed with photosensitivity reaction after photodynamic therapy using the photosensitizer, porfimer. She presented to the emergency room with a skin rash on her face, neck, and both upper and lower extremities nine days after the photodynamic therapy. She denied any outdoor activity during that period. After administration of systemic corticosteroid and anti-histamine, her skin lesions resolved completely within seven days.

Photodynamic Therapy for Endobronchial Obstruction due to Recurrent Lung Cancer : 2 Cases Report

Recurrent lung cancer with endobronchial obstruction after surgical resection due to lung cancer may lead to severe dyspnea, respiratory insufficiency and sudden death. Many palliative modalities including partial excision of endobronchial tumor, insertion of stent, and evaporation with laser, have been used for endobronchial obstruction due to recurrent endobronchial lung cancer. In photodynamic therapy (PDT), photosensitizer named photofrin, is infused intravenously at 48 hours before PDT, and diode laser of an appropriate wavelength is applied to induce destruction of tumor mass with 200~250 J/cm2. We report 2 cases of treatment using PDT for endobronchial obstruction due to recurrent endobronchial lung cancer after surgical resection.

Main factors affecting the effect of photodynamic therapy against human esophageal cancer cells in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the tumor cell-killing effect of photodynamic therapy against human esophageal cancer cells in vitro and identify the main factors affecting the effect.</p><p><b>METHODS</b>Human esophageal cancer Eca-109 cells were incubated for 24 h in vitro with hematoporphyrin derivative (HpD) and Photofrin at different concentrations prior to exposure to a light energy density of 15 J/cm(2) delivered from a DIOMED 630 PDT system. The cell killing effect was also evaluated for different HpD concentrations combined with 3 light energy densities (10, 30, and 50 J/cm(2)), respectively. The cell survival rate was measured using MTT assay, and fluorescence spectrometry was used to detect the intracellular photosensitizer fluorescence of the tumor cells after incubation with HpD for 4 h.</p><p><b>RESULTS</b>The cell survival rate after incubation with the two photosensitizers at different concentrations were significantly different, and under the 3 different light energy densities, incubation of the cells with different HpD concentrations also resulted in significantly different cell survival rates (P<0.05). At the 4 low photosensitizer concentrations and with different light energy densities, the cell survival rates were similar (P>0.05), but the 4 higher photosensitizer concentrations resulted in significant difference in the cells survival (P<0.05). Correlation analysis showed that the intracellular photosensitizer concentration was positively correlated to the photosensitizer concentrations in cell incubation (r=0.997).</p><p><b>CONCLUSION</b>When the light source remains constant, the light energy density, the kinds of photosensitizers and their concentrations are the main factors affecting the Eca-109 cell-killing effect of PDT.</p>

A Case of Photodynamic Therapy as a Curative Treatment of Early Esophageal Cancer / 대한소화기내시경학회지

Although the surgical treatment of early esophageal cancer is a well-known curative modality, less invasive endoscopic methods have attracted significant attention recently on account of the fewer postoperative complications, better quality of life and preservation of the integrity of the esophagus. Among the various endoscopic techniques employed, photodynamic therapy (PDT) has been used to allow the selective destruction of malignant tissue through a photochemical effect after the administration of a photosensitizer for curative and palliative treatment purposes. This report describes a case of a 73-year-old man with early esophageal cancer, which had been diagnosed by fluorodeoxyglucose-positron emission tomography (FDG-PET) and endoscopy and a long history of chronic pulmonary diseases such as emphysema and radiation fibrosis. The patient was cured successfully with photodynamic therapy using porfimer sodium as the photosensitizer.

Clinical Experience of Photodynamic Therapy in Five Patients with Advanced Lung Cancer / 결핵및호흡기질환

BACKGROUND: A tracheobronchial obstruction in lung cancer is associated with significant morbidity and mortality due to dyspnea, cough, hemoptysis, and recurrent respiratory infection. It is well known that one of standard treatments is photodynamic therapy (PDT) in tracheobronchial obstruction after radiotherapy, chemotherapy, and/or surgery. We reported here the role of PDT in airway obstruction in patients advanced lung cancer. METHOD: Pre-treatment protocol consisted of clinical, radiologic, and bronchoscopic examination, pulmonary function test, and assessment of Karnofsky performance status. A 2 mg/kg of porfimer sodium was injected intravenously, and then followed by cylindrical and/or interstitial irradiation with 630 nm of laser after 48 hours. The repeated bronchoscopy for debridement of necrotic tissue and re-illumination was performed after 48 hours. RESULT: Improved airway obstruction and selective tumor necrosis were achieved by photodynamic therapy in all cases. Dyspnea and performance status were improved in three cases. A purulent sputum, fever and hemoptysis were improved in one of five cases. After PDT, all patients showed temporarily aggravation of dyspnea, two of five showed febrile reaction for a few days and nobody presented photosensitivity reaction, hemoptysis and respiratory failure. CONCLUSION: Our experiences of PDT are effective in palliation of inoperable advanced lung cancer in terms of tracheobronchial obstruction.

in vitro and in vivo Photodynamic Activity Study of U-87 Human Glioma Cell with Photofrin

OBJECTIVE: The objective of this study was to determine the photodynamic therapeutic response of U-87 human glioma cell in vitro as well as in the nude rat xenograft model using photofrin as photosensitizer. MATERIAL AND METHOD: U-87 cells were cultured on 96-well culture plates, photofrin(Quadralogic Technologies Inc., Vancouver, Canada) was added into the cell culture medium at concentration of 1ng/ml, 2.5ng/ml, 5ng/ml, 10ng/ml and 20ng/ml. 24 hour after drug treatment, cells were treated with optical(632nm) irradiation of 100mJ/cm2, 200mJ/cm2 and 400mJ/cm2. Photofrin(12.5mg/kg, i.p.) was administered to 28 nude rats containing intracerebral U-87 human glioma as well as 26 normal nude rats. 48 hours after administration, animals were treated with optical irradiation(632nm) of 35J/cm2, 140J/cm2 and 280J/cm2 to exposed tumor and normal brain. The photofrin concen-tration was measured in tumor and normal brain in a separate population of animals. RESULTS: By MTT assay, there was 100% cytotoxicity at any dose of photofrin with optical irradiation of 200mJ/cm2 and 400mJ/cm2. But at the optical irradiation of 100mJ/cm2 cells were killed in dose dependent manner 28.5%, 49.1%, 54.4%, 78.2%, and 84.6% at concentration of 1ng/ml, 2.5ng/ml, 5ng/ml, 10ng/ml and 20ng/ml, respectively. Dose dependent PDT lesions in both tumor and normal brain were observed. In the tumor lesion, only superficial tissue damage was found with optical irradiation of 35J/cm2. However, in the optical irradiation group of 140J/cm2 and 280J/cm2 the volume of lesions was measured of 7.2mm3 and 14.0mm3 for treatment at 140J/cm2 and 280J/cm2, respectively. The U-87 bearing rats showed a photofrin concentration in tumor tissue of 6.53+/-2.16ng/g, 23 times higher than that found in the contralateral hemisphere of 0.28+/-0.15ng/g. CONCLUSION: Our data indicate that the U-87 human glioma in vitro and in the xenografted rats is responsive to PDT. At these doses, a reproducible injury can be delivered to human glioma in this model. Strategies to spare the normal brain collateral damage are being studied.

Cellular accumulation and biological activity of hematoporphyrin derivative(L) in comparison with photofrin II.

Hematoporphyrin derivative, a drug used in the photodynamic therapy of solid tumours was synthesized in the laboratory and was called Hpd(L). Physico-chemical and biological properties of this drug have been compared with Photofrin II, the commercially available drug. Both Hpd(L) and Photofrin II possess similar properties qualitatively. Quantitatively, Hpd(L) was half as active as Photofrin II in its efficacy in causing photodynamic cytotoxicity or in the optical densities at the absorption peaks. These differences could be due to the differences in the compositions. Hpd(L) is a non-purified complex mixture of a number of porphyrin derivatives whereas Photofrin II is a relatively purer compound consisting of di- and tri-hematoporphyrins linked through ether or ester bonds. In vitro cellular uptake and retention of these drugs has been found to be a passive process not involving energy expenditure. pH and temperature of the incubation media have been found to profoundly influence these processes, while a complex relation seems to exist between physiological state of a cell and accumulation of these photosensitizers.

Effects of photofrin II and light on cellular adenine nucleotides and their modulation.

Effects of photofrin II (PII) and light on the intra cellular nucleotide levels have been investigated using BHK-21 cell line. Results indicate that lower concentrations of photofrin II in dark increases ATP levels in a non linear manner, however, there has been no change in energy charge and levels of other nucleotides. Photoirradiation of PII-treated cells leads to a significant reduction in ATP levels and energy charge along with an increase in ATP breakdown products like ADP and AMP. The phosphorylation potential [ATP]/[ADP][Pi] also reduces upon photoirradiation of PII treated cells. Incubation conditions like pH of the medium and temperature modulate the cellular responses to a great extent.

Effects of some divalent metal ions on the aging phenomenon of hematoporphyrin and photofrin II.

Dilute aqueous solutions of hematoporphyrin (Hp) and its derivative (Hpd or PF II) have been found to undergo a transformation (aging) on keeping at room temperature leading to (i) shift of the Soret band from 395 nm to 405 nm, (ii) disappearance of visible bands I (610 nm) and IV (503 nm) and (iii) shift of the first emission band from 615 nm to 580 nm. The transformation was concentration dependent. The effects of concentration and temperature on the absorption spectra were much more pronounced in Hp than in Photofrin II (PF II). Variation of pH resulted in changes in the relative intensities of the absorption bands, possibly due to formation of different ionic species at different pH. The rate of transformation was accelerated in the presence of Zn ions (0.01 microM) and considerably increased at higher (50 microM) concentration. The effect of Cu ions was different from the effect of aging. It formed the metal-chelate even when present in very small amounts. The results (absorption and fluorescence analysis) suggest that in dilute solutions (conc. less than or equal to 2 microM) of Hp and PF II, Zn ions present in glass and water as impurity, deform the porphyrin nucleus leading to changes in the conjugated ring symmetry and hence changes in the absorption and fluorescence spectra, while in higher concentrations (greater than 2 microM) it forms the metal chelate as evidenced by their absorption and fluorescence spectra.